According to data presented at the American Society of
Hematology (ASH) meeting and the San Antonio Breast Cancer Symposium, elderly
cancer patients may be up to two times as likely as younger patients to receive
chemotherapy doses below the levels demonstrated in previously published studies
to provide the best chances for survival. Authors from both studies suggest that
suboptimal chemotherapy dosing may help explain poorer response and survival
outcomes in the elderly, and that neutropenia is a major contributor to reduced
chemotherapy doses in the elderly.
The first set of data, presented at December’s ASH meeting,
looked at the medical records of 1,761 patients with intermediate-grade
non-Hodgkin’s lymphoma to analyze the relationship between age, side effects,
and chemotherapy dose reductions. The second data analysis, presented at the San
Antonio Breast Cancer Symposium, reviewed the medical charts of 20,799 breast
cancer patients who received adjuvant chemotherapy to investigate physicians’
practice patterns and factors that contribute to chemotherapy dose variations.
"When elderly cancer patients receive full chemotherapy
doses, their survival rates are as good as younger patients. These data suggest
that doctors are not dosing older patients as optimally as they are younger
patients," said Gary Lyman, MD, MPH, Albany Medical Center. "If we
aggressively address the factors, such as neutropenia, that are causing elderly
patients to receive suboptimal chemotherapy, we may have a positive impact on
their long-term survival."
Elderly With Non-Hodgkin’s
Researchers in the Lymphoma Service of Memorial Sloan-Kettering
Cancer Center looked at the medical records of 1,761 intermediate-grade
non-Hodgkin’s lymphoma patients (49% were ³ 65 years old) from 226 community
oncology practices across the United States to determine the relationship
between age, various clinical parameters, and chemotherapy regimen
modifications. In the study, 1,514 patients (86%) were given CHOP
(cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin],
prednisone), which is the standard treatment, 141 patients (8%) received CNOP
(cyclophosphamide, mitoxantrone [Novantrone], Oncovin, prednisone), and 106
patients (6%) received CVP (cyclophosphamide, vincristine, prednisone).
The data reviewed demonstrated that older patients were more
frequently prescribed the less aggressive regimens (CNOP and CVP) than CHOP (21%
vs 7%, P < .001). Also, regardless of the regimen, older patients
were 1.8 times more likely to begin therapy at a lower dose intensity, and two
times more likely to experience dose reductions or delays than younger patients.
Overall, 43% of elderly patients and 23% of younger patients received suboptimal
The study’s authors note that research with elderly patients
has consistently shown that complete response to treatment is significantly
higher in groups who receive full chemotherapy doses than in those who receive
reduced doses. The authors further point out that while the myelotoxicity of
CHOP and CHOP-like regimens may limit the ability to deliver the standard
chemotherapy dose, dose delays or reductions may be decreased by using
granulocyte colony-stimulating factor (G-CSF [Neupogen]), which stimulates the
production of neutrophils.
"The variation in treatment between older and younger
patients we found is significant because there seems to be a relationship
between dose, complete response rates, and survival," said Andrew Zelenetz,
MD, chief of the lymphoma service at Memorial Sloan-Kettering. "The
analysis is also interesting since there is a growing opinion that proactive use
of G-CSF should be standard practice among high-risk patients over 65 years who
are expected to receive full-dose CHOP."
Contributors to Suboptimal Dosing
Researchers from Duke University, the University of Washington,
and Albany Medical College reviewed the medical records of 20,799 patients with
breast cancer from 1,243 oncology practices nationwide to determine practice
patterns with respect to relative chemotherapy dose intensity over a course of
conventional adjuvant breast cancer chemotherapy. The data review also looked at
the frequency of treatment delays, chemotherapy dose reductions, and episodes of
The data showed that more than 25% of all patients experienced
reductions in chemotherapy dose, and 43% had a treatment delay. Patients aged 65
years and older had a greater number of dose reductions (31.1% vs 24.7%, P <
.001) and treatment delays (50.4% vs 41.7%,
P < .001).
The analysis revealed that several factors contributed to the
variations in dosing, including side effects, type of regimen, and diagnosis. A
patient’s diagnosis also had an impact on dose variations. Node-negative
patients were more likely (45.9%) to receive a lower-than-standard chemotherapy
dose, compared to patients with one to four positive nodes. The regimen used
most commonly in the study was CMF (cyclophosphamide, methotrexate, fluorouracil
[5-FU]), followed by CAF (cyclophosphamide, doxorubicin [Adriamycin], 5-FU) and
AC (Adriamycin, cyclophosphamide), with the most common reductions or delays
occurring with CMF (22.2%) and CAF (24.4%).
The researchers evaluating these data are continuing their
analysis with the goal of developing a risk model to help physicians manage and
predict neutropenia. The model is expected to be completed in spring 2001.